This invention relates generally to devices and systems for measuring concentrations of ions, chemicals, biological materials, and reaction products, and more particularly, to a solid state device which employs a polyimide-based matrix as the substance-sensitive membrane and wherein the substance-sensitive membrane is installed using conventional integrated circuit fabrication techniques.
Polyimide has been used in the fabrication of integrated circuitry, particularly as a surface protection layer and as a dieleatric material between metal interconnect layers. Polyimide films are also known to be flexible, strong, and insoluble. In addition, the adherence of polyimide to materials which ordinarily are used in the fabrication of such circuit systems to form integrated circuit surfaces is well known. Examples of the materials to which polyimide adheres well include, SiO.sub.2 and Si.sub.3 N.sub.4. Surfaces formed of these materials are commonly employed in the structure of solid state sensors.
It is additionally known that polyimide exhibits significant mechanical strength, and has been used to provide enhanced mechanical support to certain structures. A polyimide layer will form a strong and mechanically rigid coupling between silicon-based materials and structural layers which are relatively weak, such as those formed of boron nitride.
Polyimide is easily incorporated into the manufacturing processes of integrated circuits. Although it is not photosensitive, it is easily patterned with conventional photoresist, employing a photomask. Moreover, polyimide is easily etched, and mask layers are easily stripped therefrom.
Silicon and polyimide have been combined in the art to produce a precursor which is useful in the production of a coating which is characterized with a strong adhesion to silicon wafer, glass, etc. In addition, polyimide precursor improves layer strength and hardness. Such precursors have been used as coatings for electronic materials, surface-protecting films, insulating films, and liquid crystal aligning agents. Polyimide precursor materials are also known to exhibit superior adhesion onto silicon wafer, glass, or the like, in addition to superior strength and hardness after baking.
In addition to its employability as a structural element in the fabrication of integrated circuit systems, polyimide has been used to form porous structures in the form of semipermeable membranes. This aspect of polyimide is unrelated to integrated circuit fabrication, and results in the production of asymmetric membranes which have a porosity appropriate for ultrafiltration and reverse osmosis, for example. Such asymmetric membranes are generally prepared by precipitation or phase inversion reaction. The membrane is dissolved in a solvent, spread into a film, and precipitated in a non-solvent. The resulting membrane is suitable for the desalination of sea water.
In one known system, asymmetric membranes from polyimides are produced by preparing membranes having asymmetric structures from acid amides of the type which can be converted to polyimides according to conventional precipitation or phase inversion reaction. The acid amide membranes are converted subsequently to polyimide membranes by thermal or chemical ring closure reaction. One known reaction scheme commences from a tetracarboxylic acid dianhydride and a diamine to form, by means of an acid amide, a polyimide. The dianhydride, or an equivalent reaction, such as an acid chloride or the like, and the diamine, in an appropriate solvent, are reacted at room temperature whereby a polyamide is obtained in the form of a soluble polymer. The polyamide is then converted to the corresponding polyimide by heating to 300.degree. C. or by chemical reaction. Alternatively, polyimides can be made by reaction of dianhydrides with other nitrogen-bearing polyfunctional compounds such as diisocyanates.
In addition to the desalination of sea water, polyimide membranes have been used in other purification processes, such as the purification of crude glyceride oil compositions, whereby the crude glyceride oil composition with impurities in the form of gum material and wax are diluted with an organic solvent and brought into communication with a semipermeable membrane formed of polyimide, under pressure. Polyimide membranes of this known type are useful in the removal of impurities which include phospholipids, such as lecithin; waxes, such as higher alcohols; organic sulfur compounds; free fatty acids; peptides; hydrocarbons; carbohydrates; lower aldehydes; lower ketones; dye compounds; and some sterols.
Polyimide membranes have found wide acceptance in the field of gas separation. Such gas separation membranes include those in which the molecular structure is such that the molecules in the polymer are unable to pack densely, and therefore have high gas permeability; those formed of aromatic polyimide prepared from polyamide acid membranes; those formed from microporous aromatic polyimide membranes, and which optionally are treated with modifying agents; those formed from a microporous aromatic polyimide support coated with an aromatic polyamide acid or aromatic polyimide; those in which the molecular structure is such that the molecules in the polymer can pack densely; those comprising as essential components thereof a saturated linear polyester or polyamide, and having copolymerized therewith benzophenone tetracarboxylic groups which are cross-linked by irradiation; those formed of aromatic polyether imides; those formed from a microporous aromatic polyimide support coated with a cross-linked silicon resin film; and aromatic polyimide reverse osmosis membranes. Polyimide membranes which are not intended for use as gas separation membranes include those formed from substituted aromatic polyimides and photochemically cross-linked compositions thereof.
In addition to the foregoing, those aromatic polyimides derived from diamines having substituents on all portions ortho to the amine function or from mixtures of aromatic diamines, particularly where some components have substituents on all positions ortho to the amine functions, exhibit high gas permeability. Such membranes are in widespread use in systems where it is necessary to select one gas over other gases in a multicomponent gas mixture. Generally, such selectivity is controlled by selection of the amount of aromatic diamines having substituents on all positions ortho to the amine functions, and/or the amounts of structurally-nonrigid dianhydrides utilized in the polyimide preparation while maintaining high gas permeability. High permeability is believed in the art to be the result of high molecular free volume in the polymer structure, and is further believed to result from the rigid nature of the rotationally hindered polymer chains.
In addition to the gas and chemical selectivity discussed hereinabove, polyimide membranes have been used in the context of biological constituents and reaction products. In the case of a system for the detection of biological reactions, it is known that a given protein will adhere to a substrate as a monomolecular layer, and that arbitrary protein layers will not adhere to the given protein layer. Instead, a protein which reacts specifically with the given protein will bond immunologically thereto. Such reactions have been monitored electronically with the use of a field effect transistor which includes a conventional source and drain, and employs in the gate region a layer of antibody specific to a specific antigen. When this layer communicates with an electrolyte solution containing the antigen, the charge of the protein surface changes as a result of the antigen-antibody reaction, thereby causing a change in the charge concentration in a semiconductor inversion layer in the field effect transistor. The monitoring is dynamic in that the time rate of change of drain current provides the measure of antigenic protein concentration. In some known immunological integrated circuit sensors, the layer of protein, such as the antibodies specific to an antigenic protein to be detected, is adsorbed on a thin insulating layer by immersing the device in a solution of such protein. However, other electrochemical devices which are useful in the clinical analysis of biological fluids employ ion-selective membrane layers.
In one known system, the ion-selective membrane layer is formed of an ionophoric material which is dispersed in a matrix of dielectric organic polymer. Generally, the matrix polymer is combined with a plasticizer to effect a certain amount of swelling of the polymer. This is oftentimes necessary to permit sufficient mobility of ion carriers through the membrane. Some of the plasticizers which have been used in such applications are dioctyl adipate, tris(2-ethylhexyl)phosphate, dibutyl sebacate, O-nitrophenyloctyl ether, diphenyl ether, dinonyl phthalate, dipentyl phthalate, di-2-nitrophenyl ether, glycerol triacetate, tributyl phosphate, and dioctyl phenyl phosphate. The ion-selective membranes are usually made by forming a solution of polymer, and optionally a plasticizer, in a volatile organic solvent, casting the solution onto the desired surface into the desired shape, and then removing the solvent by evaporation.
It is a problem with ion, chemical, or biological membranes that they generally are not compatible with integrated circuit manufacturing systems, and when they have been used in such environments, they have exhibited poor adherence to the silicon-based substrate. One prior art method for producing a substance-sensitive device which can be fabricated using conventional mass production technology employs a substance-sensitive photoresist layer which is compatible with large scale integrated circuit technology. In this known system, small quantities of substance-sensitive materials are dissolved and then fixed in the photoresist material by the exposure or non-exposure, to particular radiations, depending upon the type of photoresist. Thus, if a photoresist material is doped with a substance-sensitive material, and subsequently activated, a substance-sensitive layer will remain on the surface of the structure to which the photo-resist material is initially applied.
The solid state chemical sensor systems which have been produced in the prior art all suffer from one or more significant disadvantages. Those sensors which have been developed as replacements for traditional ion-sensitive electrodes, and which have used the same basic membrane technology as the ion-sensitive electrodes, have suffered from poor adhesion of the organic membrane to the chip surface. As indicated, the result has been the eventual formation of electrolyte shunts around the membrane, ultimately rendering the sensor inoperative. Those sensors which have utilized technology which is outside of the tradition for ion-selective electrodes, have suffered from unpredictable and/or unacceptable electrochemical properties. In addition, many of the sensor membranes, particularly those formed of polyvinyl chloride, are not well-suited to mass fabrication of sensors using integrated circuit techniques. Usually, membranes formed of polyvinyl chloride are applied manually.
The prior art has recognized that those polymer membranes which exhibit the preferred electrochemical properties are typically also those which are most incompatible with large scale integrated circuit fabrication. In particular, such membranes do not adhere well to the silicon-based substrate, and are not readily adapted to mask based or photolithographic dimensioning techniques. Moreover, such systems are not generally applicable to a multiplicity of solid state sensors simultaneously, such as at the wafer stage of production.
The problem of poor adherence has been recognized by the prior art and an effort at correcting the difficulty has been proposed. More specifically, it has been proposed in the art that the integrated circuit sensor be provided with a suspended mesh of polyimide. The polyimide is known to adhere well to the silicon-based substrate, and a polymeric membrane is formed in the void between the polyimide and the substrate by insertion while the polymeric membrane is in liquid form. Other systems have been proposed which utilize polyimide as a structural element for holding and/or supporting an ion-selective membrane in communication with the integrated circuit. All of these approaches to the basic problem of incompatibility of the membranes to solid state fabrication techniques require complex post IC manufacturing steps, often requiring manual operations, and yield results which are not reproducible from sensor to sensor.
It is, therefore, an object of this invention to provide a substance-sensitive solid state sensor which has an extended lifetime.
It is another object of this invention to provide a substance-sensitive membrane system for a solid state sensor which is possessed of excellent electrochemical properties.
It is also an object of this invention to provide a substance-sensitive membrane system for a solid state sensor which is characterized with excellent adherence to solid state sensor materials.
It is a further object of this invention to provide a substance-sensitive membrane system for a solid state sensor which can be applied to a plurality of solid state devices simultaneously using conventional integrated circuit manufacturing techniques.
It is additionally an object of this invention to provide a solid state sensor system which is not subject to the generation of disabling electrolyte shunts around the substance-sensitive membrane.
It is yet a further object of this invention to provide a solid state sensor system which is simple and low in cost.
It is also another object of this invention to provide a substance-sensitive polymeric membrane system for a solid state sensor which can be applied to a multiplicity of solid state devices simultaneously using conventional integrated circuit manufacturing techniques and which utilizes ionophoric doping to create the substance sensitivity.
It is yet an additional object of this invention to provide a substance-sensitive membrane for use with a solid state sensor and which does not require a structural layer associated therewith to maintain communication between the membrane and a solid state substrate.
It is still another object of this invention to provide a substance-sensitive solid state sensor which can be manufactured inexpensively in production quantities, and which can be adapted for industrial uses, such as monitoring treated or waste water for hardness or pollutants, on-line analysis of industrial chemicals, foodstuffs, and medicines, and low cost analytical instruments.
It is a yet further object of this invention to provide a substance-sensitive solid state sensor which can be manufactured inexpensively in production quantities, and which can be adapted for medical uses, such as monitoring of electrolytes, blood gases, and medical substrates.
It is also a further object of this invention to provide a substance-sensitive solid state sensor which can be manufactured inexpensively in production quantities, and which can be adapted for biochemical control systems.
It is additionally another object of this invention to provide a substance-sensitive solid state sensor which can be manufactured inexpensively in production quantities, and which can be adapted for patient monitoring and diagnostics.
A still further object of this invention is to provide a substance-sensitive membrane for use in a solid state sensor, wherein the membrane exhibits good adhesion to SiO.sub.2 surfaces.
An additional object of this invention is to provide a substance-sensitive membrane for use in a solid state sensor, wherein the membrane exhibits good adhesion to Si.sub.3 N.sub.4 surfaces.